Sleep and Light Therapy for Circadian Rhythm Disorder

(CARRS-P2 Trial)

Overseen By Ronette G Blake, MS

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Neuroleptics, Psoralen, Antiarrhythmics

Disqualifiers: Substance use, Psychiatric disorders, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how changes in sleep and light exposure affect the brain's reward system in teenagers, particularly those with late bedtimes. Researchers seek to determine if interventions such as adjusting sleep schedules, reducing evening blue light, and increasing morning light (morning light therapy) can improve sleep and potentially reduce the risk of substance use. Participants will either adopt a new sleep and light routine or maintain their current habits for comparison. Teens with a regular school schedule and a usual bedtime after 11:15 PM may be well-suited for this study. As an unphased study, this trial offers a unique opportunity to contribute to understanding how lifestyle changes can benefit teen health.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those who have changed their psychotropic medications in the 2 weeks before joining or plan major changes during the study. It also excludes those on medications that increase sensitivity to blue light.

What prior data suggests that these treatments are safe for adolescents?

Research shows that wearing blue blocker goggles in the evening can improve sleep quality. Excessive blue light at night disrupts sleep patterns, but blocking this light helps maintain the body's internal clock.

Bright light exposure in the morning is also part of the treatment. Studies have found that morning light therapy can adjust sleep schedules, making it easier to wake up and stay alert during the day.

Researchers will monitor participants' sleep, mood, and any substance use to track changes and assess the treatment's effectiveness, providing a better understanding of its impact on sleep and overall health.

Adjusting the sleep schedule can also be beneficial. Setting specific times to go to bed and wake up aims to create a regular sleep pattern that supports better rest and daily functioning.

Overall, treatments in this trial are well-tolerated and have shown positive effects on sleep patterns in previous studies. They are generally considered safe when used as directed. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores an innovative approach to managing Circadian Rhythm Disorder by combining light therapy and sleep scheduling. Unlike traditional treatments that may focus on medications or general sleep hygiene practices, this method specifically manipulates light exposure and sleep timing to reset the body's internal clock. The use of blue blocker goggles in the evening and bright light goggles in the morning offers a novel way to control the light spectrum and intensity, potentially leading to faster and more natural adjustments to sleep patterns. By leveraging technology to monitor sleep, mood, and substance use, this approach provides a holistic view of the impact on daily life, offering insights that could lead to more personalized and effective treatments.

What evidence suggests that this trial's treatments could be effective for circadian rhythm disorder?

This trial will compare different methods for managing circadian rhythm disorders. Research has shown that reducing blue light exposure in the evening, as participants in the "Advance/Extend Manipulation" arm will do, can improve sleep quality and duration by maintaining the body's internal clock. Blue light can interfere with melatonin, a hormone that aids sleep. Participants in this arm will also increase morning bright light exposure, which can reset the natural sleep-wake cycle and enhance sleep quality. Adjusting the sleep schedule by changing bedtime and wake-up time is another method tested in this trial to align the body's clock with natural light patterns. Together, these methods have been found to improve sleep and may help with sleep disorders related to the body's internal clock. ^{1 2 6 7 8}

Who Is on the Research Team?

Brant Hasler, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for healthy teens typically enrolled in high school, who go to bed later than 11:15 PM and are not homeschooled. They can't have metal in their body, be pregnant, have unstable medical conditions, recent changes to psychotropic meds, extreme late sleep patterns, frequent headaches or migraines, a history of substance use or serious psychiatric disorders.

Inclusion Criteria

I am enrolled in a traditional high school with live classes.

I am in good physical and mental health.

Provision of written informed consent and assent

Exclusion Criteria

I do not have any severe or unstable health conditions.

You have a serious mental health condition, like depression or bipolar disorder, that could make it hard for you to finish the study.

You have used alcohol, cannabis, or illegal drugs in the past month, or more than once a month in the past year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational Study

Participants undergo 2 weeks of home sleep monitoring followed by an overnight laboratory visit for assessments

2 weeks

1 overnight laboratory visit

Experimental Manipulation

Participants in the Late group undergo sleep and circadian rhythm manipulation for approximately 2 weeks

2 weeks

1 initial laboratory visit, followed by home-based intervention

Follow-up

Participants are monitored for changes in sleep and substance use every 6 months

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Decrease evening blue light
• Increase morning bright light
• Monitor sleep, mood, and substance use
• Sleep Scheduling

Trial Overview The study explores how manipulating sleep and circadian rhythms affects reward function in adolescents. It involves monitoring sleep patterns and mood while adjusting light exposure (more bright light in the morning; less blue light at night) and managing sleep schedules.

How Is the Trial Designed?

Group I: Advance/Extend Manipulation Experimental Treatment 4 Interventions

For \~2 weeks, Manipulation participants will advance bedtime and regularize wake time. The first night of the manipulation will be conducted in the lab under tightly-controlled experimental conditions. Participants will then go home and for the next 12 days and will be instructed to: * Sleep scheduling-- advance bedtime by 1.5 hours ( + sleep duration) * Decrease evening blue light exposure via blue blocker goggles (2 hrs before bed) * Increase morning bright light exposure via bright light goggles (30 min after rise) * Monitor sleep, mood, and substance use via smartphone-based platform and wrist actigraph

Group II: Control Active Control 1 Intervention

Control participants will complete the baseline laboratory study, then maintain their habitual sleep schedules over the next 12 days at home, with no instruction on sleep timing or light exposure. Control participants will complete smartphone-and text-based assessments and wear an actigraphy watch to monitor their sleep, behavior and sleep habits thereby controlling for effort.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Chronotherapy, which includes strategies like light therapy and sleep deprivation, has been shown to effectively reduce depressive symptoms and improve recovery in patients with depression and bipolar disorder.

Recent research indicates that combining chronotherapeutic interventions with pharmacological treatments can enhance efficacy, leading to shorter hospital stays and fewer changes in medication prescriptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of chronotherapy on depressive symptoms. Evidence-based practice. Khalifeh, AH.[2018]

A meta-analysis of 40 studies found that light interventions significantly improve sleep quality and timing in individuals with circadian rhythm disorders and neuropsychiatric conditions, with notable effects on sleep continuity and self-reported disturbances.

Avoiding evening light exposure was linked to increased total sleep time, suggesting that light management could be a beneficial strategy for enhancing sleep in psychiatric populations, warranting further research and tailored interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuro-psychiatric illness: A systematic review and meta-analysis. Faulkner, SM., Bee, PE., Meyer, N., et al.[2021]

In a study involving 18 participants, early morning light therapy using either a 10,000 Lux light box or 2,000 Lux LED blue-enriched glasses significantly improved alertness, cognition, and mood after a night of complete sleep deprivation.

Both light therapy devices were equally effective and well-tolerated, suggesting that early light exposure can be a practical solution to counteract the negative effects of sleep deprivation, especially for shift workers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Light therapy with boxes or glasses to counteract effects of acute sleep deprivation. Comtet, H., Geoffroy, PA., Kobayashi Frisk, M., et al.[2021]

In a study of 203 depressed patients, those with a preference for being active in the evening (evening chronotypes) showed significantly better treatment outcomes when attending morning sessions compared to afternoon sessions.

A positive correlation was found between increased morningness after four weeks of treatment and decreased depression scores, suggesting that aligning treatment times with patients' chronotypes may enhance therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morningness-eveningness scores predict outcomes differentially for depressed patients attending morning vs. afternoon day treatment streams. Levitan, RD., Klein, R., Bakshi, N., et al.[2020]

In a pilot study involving 10 suicidal inpatients with unipolar depression, the use of Triple Chronotherapy (total sleep deprivation, sleep phase advance, and bright light therapy) led to significant reductions in depression and suicidality, with HAM17 scores dropping from 24.7 to 9.4 and CSSRS scores from 19.5 to 7.2 by day five.

The results suggest that Triple Chronotherapy is a feasible and tolerable intervention for acutely suicidal and depressed patients, although the study's small size and lack of a control group highlight the need for further randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study. Sahlem, GL., Kalivas, B., Fox, JB., et al.[2022]

Using amber-tinted safety glasses to block blue light at night may create a 'virtual darkness' that helps stabilize circadian rhythms, which is beneficial for patients with bipolar disorder and sleep disturbances.

A preliminary case series suggests that this approach can reduce sleep-onset latency in some bipolar disorder patients, indicating potential for broader applications in treating insomnia and circadian rhythm disruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dark therapy for bipolar disorder using amber lenses for blue light blockade. Phelps, J.[2022]

Dynamic light exposure, which changes spectrum and intensity throughout the day, enhances melatonin secretion and reduces sleep latency compared to static light, suggesting it may improve sleep initiation.

In a study with 14 healthy men, while dynamic light did not significantly affect cognitive performance or sleep quality, it was associated with increased melatonin levels in the evening, indicating potential benefits for sleep regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing color and intensity of LED lighting across the day impacts on circadian melatonin rhythms and sleep in healthy men. Stefani, O., Freyburger, M., Veitz, S., et al.[2021]

Circadian rhythm abnormalities may play a significant role in the development of mood disorders like bipolar disorder, major depression, and seasonal affective disorder, suggesting that treatments targeting these rhythms could be effective.

Current treatments such as total sleep deprivation and bright light therapy may work by resetting the circadian clock, and some mood stabilizers and antidepressants might also exert their effects through similar mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian genes, rhythms and the biology of mood disorders. McClung, CA.[2022]

In a pilot study of 44 unipolar depressed outpatients, triple chronotherapy showed a higher Week 1 remission rate (25.0%) compared to an alternative protocol (6.7%), although this difference was not statistically significant.

The study indicated that triple chronotherapy is feasible and well-tolerated in this population, suggesting the need for larger trials to better assess its efficacy in treating unipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled trial assessing the acute efficacy of triple chronotherapy in unipolar depression. Yuen, LD., Chen, Y., Stewart, JW., et al.[2022]

In a study of 33 medical inpatients, morning bright light therapy combined with evening short-wavelength filter glasses improved sleep quality, leading to fewer night awakenings and earlier wake times compared to standard care.

Patients receiving the light therapy reported lower sleepiness and higher mood levels during the morning hours, indicating that this treatment is both effective and well-tolerated for enhancing daytime alertness and emotional well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Morning Light Glasses and Night Short-Wavelength Filter Glasses on Sleep-Wake Rhythmicity in Medical Inpatients. Formentin, C., Carraro, S., Turco, M., et al.[2020]

Light therapy is an effective, evidence-based treatment for Seasonal Affective Disorder, influencing circadian rhythms that affect sleep, mood, and cognition, based on 40 years of clinical trials.

For optimal results, light therapy should use devices that provide 10,000 lux of white light for 30-60 minutes in the early morning, with ongoing monitoring to adjust treatment as needed and manage any side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CME: Light Therapy: Why, What, for Whom, How, and When (And a Postscript about Darkness). Wirz-Justice, A., Terman, AM.[2022]

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A systematic review and meta-analysis on light therapy for ... The results showed that light therapy significantly improved the total sleep time (TST) (MD = 32.54, p < 0.00001) and sleep efficiency (SE) (MD ...

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No Light at Night and Bright Light in the Morning Excessive evening and nighttime blue light exposure can alter the timing of circadian rhythms and delay sleep onset.

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Evening use of light-emitting eReaders negatively affects ... We found that the use of these devices before bedtime prolongs the time it takes to fall asleep, delays the circadian clock, suppresses levels of the sleep- ...